[89Zr]ZrDFO-CR011 positron emission tomography correlates with response to glycoprotein non-metastatic melanoma B-targeted therapy in triple negative breast cancer

There is a need for prognostic markers to select patients most likely to benefit from antibody drug conjugate (ADC) therapy. We quantified the relationship between pre-treatment positron emission tomography (PET) imaging of glycoprotein non-metastatic melanoma B (gpNMB) with 89Zr-labeled anti-gpNMB antibody ([89Zr]ZrDFO-CR011) and response to ADC therapy (CDX-011) in triple negative breast cancer (TNBC). First, we compared different PET imaging metrics and found that standardized uptake values (SUV) and tumor-to-heart SUV ratios (SUVR) were sufficient to delineate differences in radiotracer uptake in the tumor of four different cell- and patient-derived tumor models and achieved high standardized effect sizes. These tumor models with varying levels of gpNMB expression were imaged with [89Zr]ZrDFO-CR011 followed by treatment with a single bolus injection of CDX-011. The percent change in tumor volume relative to baseline (% CTV) was then correlated with SUVmean of [89Zr]ZrDFO-CR011 uptake in the tumor. All gpNMB-positive tumor models responded to CDX-011 over 6 weeks of treatment, except one patient-derived tumor re-grew after 4 weeks of treatment. As expected, the gpNMB-negative tumor increased in volume by 130 {plus minus} 59 % at endpoint. The magnitude of pre-treatment SUV had the strongest inverse correlation with the % CTV at 2 - 4 weeks after treatment with CDX-011 (Spearman ρ = -0.8). However, pre-treatment PET imaging with [89Zr]ZrDFO-CR011 did not inform on which tumor types will re-grow over time. Other methods will be needed to predict resistance to treatment.